Determining the Long-Term Effects of Prenatal Dexamethasone Treatment in Children With 21-Hydroxylase Deficiency and Their Mothers

Long-Term Outcome in Offspring and Mothers of Dexamethasone-Treated Pregnancies at Risk for Classical Congenital Adrenal Hyperplasia Owing to 21-Hydroxylase Deficiency

Congenital adrenal hyperplasia (CAH) is a genetic disorder that affects the amount of steroids that the body forms. The most common form of CAH is 21-hydroxylase deficiency (21OHD), which leads to cortisol deficiency and causes the development of mature masculine characteristics in newborn, prepubescent, and grown females, and prepubescent males. Prenatal treatment with dexamethasone, a corticosteroid, has been shown to reduce the masculinization of genitalia. However, the long-term effects of dexamethasone on the children who received it as fetuses and on mothers who were exposed to it while they were pregnant have not been determined. This study will investigate potential long-term adverse side effects of prenatal dexamethasone treatment in children and young adults who received dexamethasone as fetuses and their mothers who were exposed to it during pregnancy.

Study Overview

• Status: Unknown
• Conditions: Adrenal Hyperplasia, Congenital

Detailed Description

CAH is a genetic steroidogenesis disorder. The most common form, 21OHD, leads to cortisol deficiency and, in turn, an excess of androgen, a hormone that promotes the development and maintenance of male sex characteristics. As a result of this androgen excess, prepubescent males and newborn, prepubescent, and grown females exhibit mature masculine characteristics. Prenatal treatment with dexamethasone, a corticosteroid that decreases androgen levels, has been shown to prevent the development of abnormal genitalia in female infants. The long-term effects of this treatment, however, have not been evaluated. This study will determine whether prenatal dexamethasone treatment causes any long-term side effects by examining children and young adults who received dexamethasone as fetuses and their mothers, who were exposed to dexamethasone while pregnant.

This study has three parts. In Part 1 of the study, participants will provide written consent for release of their medical records from their physicians. Participants' physicians will then complete a medical form and/or provide copies of selected medical records for each participant. Parts 2 and 3 can be completed in 1 day. In Part 2 of the study, participants will complete questionnaires in their homes. Participants will answer questions about the following experiences: medical procedures, such as hormone treatment and genital surgery; education; work; hobbies; play activities and chores during childhood; identification with the male or female gender; relationships with parents; interest in being a parent; and overall adjustment. Part 3 of the study will consist of neuropsychological testing at the study site. This testing will focus on memory, attention, and overall cognitive abilities.

• Study Type: Observational
• Enrollment (Anticipated): 233

Contacts and Locations

• Study Contact: Name: Claire Gilbert; Email: claire.gilbert@mssm.edu

Study Locations

• Brazil
  • SP
    • Sao Paolo, SP, Brazil
      • Not yet recruiting
      • University of Sao Paolo
      • Contact: Ivo Arnhold, MD; Phone Number: 55-11-3069-7512; Email: iarnhold@usp.br
      • Principal Investigator: Ivo Arnhold, MD
      • Sub-Investigator: Berenice Mendonca, MD, PhD
• France
  • Lyon, France
    • Recruiting
    • University of Lyon
    • Contact: Pierre Chatelain, MD; Phone Number: 04-72-38-58-73; Email: pierre.chatelain@chu-lyon.fr
    • Principal Investigator: Pierre Chatelain, MD
    • Sub-Investigator: Maguelone Forest, MD, PhD
    • Sub-Investigator: Michael David, MD
• United States
  • New York
    • New York, New York, United States, 10029
      • Recruiting
      • Mount Sinai School of Medicine
      • Contact: Claire Gilbert, MS; Phone Number: 212-241-7099; Email: claire.gilbert@mssm.edu
      • Principal Investigator: Maria I. New, MD
      • Sub-Investigator: Madeline Harbison, MD
      • Sub-Investigator: Karen Lin-Su, MD
      • Sub-Investigator: Robert Wilson, PhD
      • Sub-Investigator: Saroj Nimkarn, MD
      • Sub-Investigator: Susan Baker, PhD
      • Sub-Investigator: Heino Meyer-Bahlburg, PhD
  • Texas
    • Dallas, Texas, United States, 75390
      • Not yet recruiting
      • University of Texas Southwestern Medical Center
      • Contact: Jean Wilson, MD; Phone Number: 214-648-3494; Email: jean.wilson@utsouthwestern.edu
      • Principal Investigator: Jean Wilson, MD
      • Sub-Investigator: Richard Auchus, MD, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 12 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Participants in this study will include children who received prenatal dexamethasone treatment as fetuses and their mothers.

Description

Inclusion Criteria:

For all participants:

• English-speaking
• Has undergone DNA testing for mutations in the CYP21A2 gene

For children who received prenatal dexamethasone treatment:

• Genetic confirmation of 21OHD diagnosis
• Received full or partial prenatal dexamethasone treatment

For children in the control group:

• Did not receive prenatal dexamethasone treatment

For mothers:

• History of at-risk pregnancy for a fetus affected with 21OHD
• Genetic confirmation of child's diagnosis

Exclusion Criteria:

• Any mental disorder that could prevent understanding of study materials
• Current or past steroid use for reasons other than CAH (i.e., asthma, lupus, rheumatoid arthritis)

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Control
• Time Perspectives: Prospective

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort
Category 1, Group 1; Children who have 21OHD and received prenatal dexamethasone treatment
Category 1, Group 2; Children who have 21OHD and did not receive prenatal dexamethasone treatment (control)
Category 2; Mothers of children who received prenatal dexamethasone treatment

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Prevalence of hypertension and obesity	Throughout the study
"Normal" masculinization of unaffected females treated prenatally with dexamethasone	Throughout the study
Normal masculinization of male fetuses partially treated prenatally with dexamethasone	Throughout the study
Memory-related cognitive function	Throughout the study

Collaborators and Investigators

• Sponsor: Office of Rare Diseases (ORD)
• Investigators: Study Chair: Maria I. New, MD, Icahn School of Medicine at Mount Sinai

Study record dates

Study Major Dates

• Study Start: January 1, 2008
• Primary Completion (Anticipated): July 1, 2009
• Study Completion (Anticipated): July 1, 2009

Study Registration Dates

• First Submitted: January 31, 2008
• First Submitted That Met QC Criteria: February 5, 2008
• First Posted (Estimate): February 18, 2008

Study Record Updates

• Last Update Posted (Estimate): December 9, 2008
• Last Update Submitted That Met QC Criteria: December 8, 2008
• Last Verified: December 1, 2008

More Information

Terms related to this study

• Keywords: CAH; 21-hydroxylase deficiency; 21OHD
• Additional Relevant MeSH Terms: Pathologic Processes; Metabolic Diseases; Endocrine System Diseases; Gonadal Disorders; Disorders of Sex Development; Urogenital Abnormalities; Congenital Abnormalities; Genetic Diseases, Inborn; Metabolism, Inborn Errors; Adrenal Gland Diseases; Steroid Metabolism, Inborn Errors; Hyperplasia; Adrenal Hyperplasia, Congenital; Adrenogenital Syndrome
• Other Study ID Numbers: RDCRN 5610